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Abstract Background Degeneration of the motoneuron and neuromuscular junction (NMJ) and loss of motor units (MUs) contribute to age‐related muscle wasting and weakness associated with sarcopenia. However, these features have not been comprehensively investigated in humans. This study aimed to compare neuromuscular system integrity and function at different stages of sarcopenia, with a particular focus on NMJ stability and MU properties. Methods We recruited 42 young individuals (Y) (aged 25.98 ± 4.6 years; 57% females) and 88 older individuals (aged 75.9 ± 4.7 years; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People 2. In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and MU potential properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) and blood samples were obtained. Muscle biopsies were collected in a subgroup of 16 Y and 52 older participants. Results Thirty‐nine older individuals were non‐sarcopenic (NS), 31 pre‐sarcopenic (PS) and 18 sarcopenic (S). A gradual decrease in quadriceps force, cross‐sectional area and appendicular lean mass was observed across the different stages of sarcopenia (for all P

Purpose: This study aimed to non-invasively test the hypothesis that (a) short-term lower limb unloading would induce changes in the neural control of force production (based on motor units (MUs) properties) in the vastus lateralis muscle and (b) possible changes are reversed by active recovery (AR). Methods: Ten young males underwent 10 days of unilateral lower limb suspension (ULLS) followed by 21 days of AR. During ULLS, participants walked exclusively on crutches with the dominant leg suspended in a slightly flexed position (15°–20°) and with the contralateral foot raised by an elevated shoe. The AR was based on resistance exercise (leg press and leg extension) and executed at 70% of each participant's 1 repetition maximum, 3 times/week. Maximal voluntary isometric contraction (MVC) of knee extensors and MUs properties of the vastus lateralis muscle were measured at baseline, after ULLS, and after AR. MUs were identified using high-density electromyography during trapezoidal isometric contractions at 10%, 25%, and 50% of the current MVC, and individual MUs were tracked across the 3 data collection points. Results: We identified 1428 unique MUs, and 270 of them (18.9%) were accurately tracked. After ULLS, MVC decreased by 29.77%, MUs absolute recruitment/derecruitment thresholds were reduced at all contraction intensities (with changes between the 2 variables strongly correlated), while discharge rate was reduced at 10% and 25% but not at 50% MVC. Impaired MVC and MUs properties fully recovered to baseline levels after AR. Similar changes were observed in the pool of total as well as tracked MUs. Conclusion: Our novel results demonstrate, non-invasively, that 10 days of ULLS affected neural control predominantly by altering the discharge rate of lower-threshold but not of higher-threshold MUs, suggesting a preferential impact of disuse on motoneurons with a lower depolarization threshold. However, after 21 days of AR, the impaired MUs properties were fully restored to baseline levels, highlighting the plasticity of the components involved in neural control.

Abstract The aim of this study was to investigate the reliability of panoramic ultrasound (US) imaging and agreement with magnetic resonance imaging (MRI) for assessing the average lumbar multifidus anatomical cross-sectional area between the lumbar vertebral bodies L3–L5 (i.e., LMF ACSAL3–L5). US and MRI scans of 20 male youth competitive alpine skiers were collected. To test the intra- and interrater reliability of US, transversal panoramic scans were analyzed on two different days by the same rater and the analysis of the first day was compared with the analysis of a second rater. To examine the agreement between US and MRI, Bland–Altman analysis was performed. Intrarater reliability was excellent, and interrater reliability was weak to good for both sides. The bias between MRI and US was − 0.19 ± 0.90 cm2 (2.68 ± 12.30%) for the left side and − 0.04 ± 0.98 cm2 (− 1.11 ± 12.93%) for the right side (i.e., for both sides US slightly overestimated LMF ACSAL3–L5 on average). The limits of agreement were − 1.95 to 1.57 cm2 (− 26.70 to 21.30%) for the left side and − 1.95 to 1.88 cm2 (− 26.46 to 24.24%) for the right side. Panoramic US imaging may be considered a method with excellent intrarater and weak to good interrater reliability for assessing LMF ACSAL3–L5. Comparison with MRI showed large individual differences in some cases, but an acceptable bias between the two imaging modalities.

Abstract Ultrasound‐derived measurements of muscle fascicle length (FL) are often used to infer increases (chronic stretch or training) or decreases (muscle disuse or aging) in serial sarcomere number (SSN). Whether FL adaptations measured via ultrasound can truly approximate SSN adaptations has not been investigated. We casted the right hindlimb of 15 male Sprague–Dawley rats in a dorsiflexed position (i.e., stretched the plantar flexors) for 2 weeks, with the left hindlimb serving as a control. Ultrasound images of the soleus, lateral gastrocnemius (LG), and medial gastrocnemius (MG) were obtained with the ankle at 90° and full dorsiflexion for both hindlimbs pre and post‐cast. Following post‐cast ultrasound measurements, legs were fixed in formalin with the ankle at 90°, then muscles were dissected and fascicles were teased out for measurement of sarcomere lengths via laser diffraction and calculation of SSN. Ultrasound detected an 11% increase in soleus FL, a 12% decrease in LG FL, and an 8–11% increase in MG FL for proximal fascicles and at full dorsiflexion. These adaptations were partly reflected by SSN adaptations, with a 6% greater soleus SSN in the casted leg than the un‐casted leg, but no SSN differences for the gastrocnemii. Weak relationships were observed between ultrasonographic measurements of FL and measurements of FL and SSN from dissected fascicles. Our results showed that ultrasound‐derived FL measurements can overestimate an increase in SSN by ∼5%. Future studies should be cautious when concluding a large magnitude of sarcomerogenesis from ultrasound‐derived FL measurements, and may consider applying a correction factor.

Introduction: The mechanical properties of skeletal muscle are indicative of its capacity to perform physical work, state of disease, or risk of injury. Ultrasound shear wave elastography conducts a quantitative analysis of a tissue’s shear stiffness, but current implementations only provide two-dimensional measurements with limited spatial extent. We propose and assess a framework to overcome this inherent limitation by acquiring numerous and contiguous measurements while tracking the probe position to create a volumetric scan of the muscle. This volume reconstruction is then mapped into a parameterized representation in reference to geometric and anatomical properties of the muscle. Such an approach allows to quantify regional differences in muscle stiffness to be identified across the entire muscle volume assessed, which could be linked to functional implications.Methods: We performed shear wave elastography measurements on the vastus lateralis (VL) and the biceps femoris long head (BFlh) muscle of 16 healthy volunteers. We assessed test-retest reliability, explored the potential of the proposed framework in aggregating measurements of multiple subjects, and studied the acute effects of muscular contraction on the regional shear wave velocity post-measured at rest.Results: The proposed approach yielded moderate to good reliability (ICC between 0.578 and 0.801). Aggregation of multiple subject measurements revealed considerable but consistent regional variations in shear wave velocity. As a result of muscle contraction, the shear wave velocity was elevated in various regions of the muscle; showing pre-to-post regional differences for the radial assessement of VL and longitudinally for BFlh. Post-contraction shear wave velocity was associated with maximum eccentric hamstring strength produced during six Nordic hamstring exercise repetitions.Discussion and Conclusion: The presented approach provides reliable, spatially resolved representations of skeletal muscle shear wave velocity and is capable of detecting changes in three-dimensional shear wave velocity patterns, such as those induced by muscle contraction. The observed systematic inter-subject variations in shear wave velocity throughout skeletal muscle additionally underline the necessity of accurate spatial referencing of measurements. Short high-effort exercise bouts increase muscle shear wave velocity. Further studies should investigate the potential of shear wave elastography in predicting the muscle’s capacity to perform work.

Abstract The purpose of this study was to compare the effects of electromagnetic resistance alone, as well as in combination with variable resistance or accentuated eccentric methods, with traditional dynamic constant external resistance exercise on myoelectric activity during elbow flexion. The study employed a within-participant randomized, cross-over design whereby 16 young, resistance-trained male and female volunteers performed elbow flexion exercise under each of the following conditions: using a dumbbell (DB); using a commercial electromagnetic resistance device (ELECTRO); variable resistance (VR) using a setting on the device that attempts to match the level of resistance to the human strength curve, and; eccentric overload (EO) using a setting on the device that increases the load by 50% on the eccentric portion of each repetition. Surface electromyography (sEMG) was obtained for the biceps brachii, brachioradialis and anterior deltoid on each of the conditions. Participants performed the conditions at their predetermined 10 repetition maximum. " The order of performance for the conditions was counterbalanced, with trials separated by a 10-min recovery period. The sEMG was synced to a motion capture system to assess sEMG amplitude at elbow joint angles of 30°, 50°, 70°, 90°, 110°, with amplitude normalized to the maximal activation. The anterior deltoid showed the largest differences in amplitude between conditions, where median estimates indicated greater concentric sEMG amplitude (~ 7–10%) with EO, ELECTRO and VR compared with DB. Concentric biceps brachii sEMG amplitude was similar between conditions. In contrast, results indicated a greater eccentric amplitude with DB compared to ELECTRO and VR, but unlikely to exceed a 5% difference. Data indicated a greater concentric and eccentric brachioradialis sEMG amplitude with DB compared to all other conditions, but differences were unlikely to exceed 5%. The electromagnetic device tended to produce greater amplitudes in the anterior deltoid, while DB tended to produce greater amplitudes in the brachioradialis; amplitude for the biceps brachii was relatively similar between conditions. Overall, any observed differences were relatively modest, equating to magnitudes of ~ 5% and not likely greater than 10%. These differences would seem to be of minimal practical significance.

Abstract Background Inactivity and unloading induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. Bed rest is a model to study the impact of inactivity on the musculoskeletal system. It not only provides information for bed‐ridden patients care, but it is also a ground‐based spaceflight analogue used to mimic the challenges of long space missions for the human body. In both cases, it would be desirable to develop a panel of biomarkers to monitor muscle atrophy in a minimally invasive way at point of care to limit the onset of muscle loss in a personalized fashion. Methods We applied mass spectrometry‐based proteomics to measure plasma protein abundance changes in response to 10 days of bed rest in 10 young males. To validate the correlation between muscle atrophy and the significant hits emerging from our study, we analysed in parallel, with the same pipeline, a cohort of cancer patients with or without cachexia and age‐matched controls. Our analysis resulted in the quantification of over 500 proteins. Results Unloading affected plasma concentration of proteins of the complement cascade, lipid carriers and proteins derived from tissue leakage. Among the latter, teneurin‐4 increased 1.6‐fold in plasma at bed rest day 10 (BR10) compared with BR0 (6.E9 vs. 4.3E9, P = 0.02) and decreased to 0.6‐fold the initial abundance after 2 days of recovery at normal daily activity (R + 2, 2.7E9, P = 3.3E‐4); the extracellular matrix protein lumican was decreased to 0.7‐fold (1.2E9 vs. 8.5E8, P = 1.5E‐4) at BR10 and remained as low at R + 2. We identified six proteins distinguishing subjects developing unloading‐mediated muscle atrophy (decrease of >4% of quadriceps cross‐sectional area) from those largely maintaining their initial muscle mass. Among them, transthyretin, a thyroid hormone‐binding protein, was significantly less abundant at BR10 in the plasma of subjects with muscle atrophy compared with those with no atrophy (1.6E10 vs. 2.6E10, P = 0.001). Haptoglobin‐related protein was also significantly reduced in the serum of cancer patients with cachexia compared with that of controls. Conclusions Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions. The panel of significant proteomic differences distinguishing atrophy‐prone and atrophy‐resistant subjects after 10 days of bed rest need to be tested in a larger cohort to validate their potential to predict inactivity‐triggered muscle loss in humans.

From a preventative perspective, leg axis and core stabilization capacities are important for soccer players and alpine skiers; however, due to different sport-specific demands, the role of laterality clearly differs and may result in functional long-term adaptations. The aims of this study are 1) to determine whether there are differences in leg axis and core stability between youth soccer players and alpine skiers and 2) between dominant and non-dominant sides, and 3) to explore the outcomes of applying common sport-specific asymmetry thresholds to these two distinct cohorts. Twenty-one highly trained/national-level soccer players (16.1 years, 95% CI: 15.6, 16.5) and 61 alpine skiers (15.7 years, 95% CI: 15.6, 15.8) participated in this study. Using a marker-based 3D motion capture system, dynamic knee valgus was quantified as the medial knee displacement (MKD) during drop jump landings, and core stability was quantified as the vertical displacement during deadbug bridging exercise (DBBdisplacement). For the analysis of sports and side differences, a repeated-measures multivariate analysis of variance was used. For the interpretation of laterality, coefficients of variation (CV) and common asymmetry thresholds were applied. There were no differences in MKD or DBBdisplacement between soccer players and skiers or between the dominant and non-dominant sides, but there was an interaction effect side*sports for both variables (MKD: p = 0.040, η2p = 0.052; DBBdisplacement: p = 0.025, η2p = 0.061). On average, MKD was larger on the non-dominant side and DBBdisplacement laterality on the dominant side in soccer players, whereas this pattern was reversed in alpine skiers. Despite similar absolute values and asymmetry magnitudes of dynamic knee valgus and deadbug bridging performance in youth soccer players and alpine skiers, the effect on the direction of laterality was opposite even though much less pronounced. This may imply that sport-specific demands and potential laterality advantages should be considered when dealing with asymmetries in athletes.

Background: Eccentric exercise increases muscle fascicle lengths; however, the mechanisms behind this adaptation are still unknown. This study aimed to determine whether biceps femoris long head (BFlh) fascicle length increases in response to 3 weeks of eccentric exercise training are the result of an in-series addition of sarcomeres within the muscle fibers. Methods: Ten recreationally active participants (age = 27 ± 3 years; mass = 70 ± 14 kg; height = 174 ± 9 cm; mean ± SD) completed 3 weeks of Nordic hamstring exercise (NHE) training on a custom exercise device that was instrumented with load cells. We collected in vivo sarcomere and muscle fascicle images of the BFlh in 2 regions (central and distal) by using microendoscopy and 3 dimension ultrasonography. We then estimated sarcomere length, sarcomere number, and fascicle length before and after the training intervention. Results: Eccentric knee flexion strength increased after the training (15%; p < 0.001; ηp2 = 0.75). Further, we found a significant increase in fascicle length (21%; p < 0.001; ηp2 = 0.81) and sarcomere length (17%; p < 0.001; ηp2 = 0.90) in the distal but not in the central portion of the muscle. The estimated number of sarcomeres in series did not change in either region. Conclusion: Fascicle length adaptations appear to be heterogeneous in the BFlh in response to 3 weeks of NHE training. An increase in sarcomere length, rather than the addition of sarcomeres in series, appears to underlie increases in fascicle length in the distal region of the BFlh. The mechanism driving regional increases in fascicle and sarcomere length remains unknown, but we speculate that it may be driven by regional changes in the passive tension of muscle or connective tissue adaptations.

Lower extremity injuries are common in competitive alpine skiers, and the knee and lower leg are often affected. The hamstring muscles, especially the biceps femoris long head (BFlh), can stabilize the knee and the hip and may counteract various adverse loading patterns during typical mechanisms leading to severe lower extremity injuries. The aim of the present study was to describe BFlh morphology in youth competitive alpine skiers in relation to sex, age and biological maturation and to investigate its association with the occurrence of traumatic lower extremity injuries in the upcoming season. 95 youth skiers underwent anthropometric measurements, maturity offset estimations and ultrasound assessment, followed by 12-months prospective injury surveillance. Unpaired t tests showed that the two sexes did not differ in BFlh morphology, including fascicle length (Lf), pennation angle (PA), muscle thickness (MT) and average anatomical cross-sectional area (ACSAavg). In contrast, U16 skiers had longer fascicles than U15 skiers (9.5 ± 1.3 cm vs 8.9 ± 1.3 cm, p < 0.05). Linear regression analyses revealed that maturity offset was associated with Lf (R2 = 0.129, p < 0.001), MT (R2 = 0.244, p < 0.001) and ACSAavg (R2 = 0.065, p = 0.007). No association was found between maturity offset and PA (p = 0.524). According to a binary logistic regression analysis, ACSAavg was significantly associated with the occurrence of traumatic lower extremity injuries (Chi-square = 4.627, p = 0.031, RNagelkerke2 = 0.064, Cohen f = 0.07). The present study showed that BFlh morphology is age- and biological maturation-dependent and that BFlh ACSAavg can be considered a relevant modifiable variable associated with lower extremity injuries in youth competitive alpine skiers.

High end ultrasonography devices lack in portability and are expensive. We investigated the agreement and reliability of a handheld and portable ultrasound system for human lower limb muscle architecture measurements. We captured ultrasound images of the rectus femoris (RF), vastus lateralis (VL) and gastrocnemius medialis (GM) in 36 active healthy participants (15 female, 21 male) at 50% of muscle length using the handheld Lumify (L12-4, linear-array 37 mm, Philips Healthcare, Amsterdam, Netherlands) and a high-end laboratory device (ACUSON Juniper, linear-array 54 mm, 12L3, SIEMENS Healthineers, Erlangen, Germany). We compared measurements of muscle fascicle length, pennation angle and thickness. To assess inter-session reliability of the Lumify system, participants were measured twice within 1 week. Comparing RF architecture measurements of both devices resulted in intra-class correlations (ICCs) ranging from 0.46–0.82 and standardized mean difference (SMDs) ranging from −0.45–0.05. For VL, ICCs ranged from 0.60–0.89 and SMDs ranged from −0.11–0.13. ICCs and SMDs for the GM ranged from 0.82–0.86 and −0.07–0.07. Calculating inter-session reliability for RF resulted in ICCs ranging from 0.44–0.76 and SMDs ranging from −0.38–0.15. For VL, ICCs and SMDs ranged from 0.57–0.75 and −0.13–0.02. ICCs for GM ranged from 0.75–0.92 and SMDs ranged from −0.15–0.16. Measurement of muscle thickness demonstrated the highest agreement (ICC ≥0.82) and reliability (ICC ≥0.75) across all muscles. The Lumify system was comparable to a high-end device and reliable for GM measurements. However, agreement and reliability were lower for the RF and VL. Of all evaluated architectural parameters, muscle thickness exhibited highest agreement and reliability.

Abstract Background The assessment of muscle mass is a key determinant of the diagnosis of sarcopenia. We introduce for the first time an ultrasound imaging method for diagnosing sarcopenia based on changes in muscle geometric proportions. Methods Vastus lateralis muscle fascicle length (Lf) and thickness (Tm) were measured at 35% distal femur length by ultrasonography in a population of 279 individuals classified as moderately active elderly (MAE), sedentary elderly (SE) (n = 109), mobility impaired elderly (MIE) (n = 43), and in adult young controls (YC) (n = 60). The ratio of Lf/Tm was calculated to obtain an ultrasound index of the loss of muscle mass associated with sarcopenia (USI). In a subsample of elderly male individuals (n = 76) in which corresponding DXA measurements were available (MAE, n = 52 and SE, n = 24), DXA‐derived skeletal muscle index (SMI, appendicular limb mass/height2) was compared with corresponding USI values. Results For both young and older participants, USI values were found to be independent of sex, height and body mass. USI values were 3.70 ± 0.52 for YC, 4.50 ± 0.72 for the MAE, 5.05 ± 1.11 for the SE and 6.31 ± 1.38 for the MIE, all significantly different between each other (P 5.82 were classified as severely sarcopenic (prevalence 9.6%). The DXA‐derived SMI was found to be significantly correlated with USI (r = 0.61, P

Abstract As the excitation–contraction coupling is inseparable during voluntary exercise, the relative contribution of the mechanical and neural input on hypertrophy-related molecular signalling is still poorly understood. Herein, we use a rat in-vivo strength exercise model with an electrically-induced standardized excitation pattern, previously shown to induce a load-dependent increase in myonuclear number and hypertrophy, to study acute effects of load on molecular signalling. We assessed protein abundance and specific phosphorylation of the four protein kinases FAK, mTOR, p70S6K and JNK after 2, 10 and 28 min of a low- or high-load contraction, in order to assess the effects of load, exercise duration and muscle-type on their response to exercise. Specific phosphorylation of mTOR, p70S6K and JNK was increased after 28 min of exercise under the low- and high-load protocol. Elevated phosphorylation of mTOR and JNK was detectable already after 2 and 10 min of exercise, respectively, but greatest after 28 min of exercise, and JNK phosphorylation was highly load-dependent. The abundance of all four kinases was higher in TA compared to EDL muscle, p70S6K abundance was increased after exercise in a load-independent manner, and FAK and JNK abundance was reduced after 28 min of exercise in both the exercised and control muscles. In conclusion, the current study shows that JNK activation after a single resistance exercise is load-specific, resembling the previously reported degree of myonuclear accrual and muscle hypertrophy with repetition of the exercise stimulus.

Abstract Open-access scripts to perform muscle anatomical cross-sectional area (ACSA) evaluation in ultrasound images are currently unavailable. This study presents a novel semi-automatic ImageJ script (named “ACSAuto”) for quantifying the ACSA of lower limb muscles. We compared manual ACSA measurements from 180 ultrasound scans of vastus lateralis (VL) and rectus femoris (RF) muscles to measurements assessed by the ACSAuto script. We investigated inter- and intra-investigator reliability of the script. Consecutive-pairwise intra-class correlations (ICC) and standard error of measurement (SEM) with 95% compatibility interval were calculated. Bland–Altman analyses were employed to test the agreement between measurements. Comparing manual and ACSAuto measurements, ICCs and SEMs ranged from 0.96 to 0.999 and 0.12 to 0.96 cm2 (1.2–5.9%) and mean bias was smaller than 0.5 cm2 (4.3%). Inter-investigator comparison revealed ICCs, SEMs and mean bias ranging from 0.85 to 0.999, 0.07 to 1.16 cm2 (0.9–7.6%) and − 0.16 to 0.66 cm2 (− 0.6 to 3.2%). Intra-investigator comparison revealed ICCs, SEMs and mean bias between 0.883–0.998, 0.07–0.93 cm2 (1.1–7.6%) and − 0.80 to 0.15 cm2 (− 3.4 to 1.8%). Image quality needs to be high for efficient and accurate ACSAuto analyses. Taken together, the ACSAuto script represents a reliable tool to measure RF and VL ACSA, is comparable to manual analysis and can reduce time needed to evaluate ultrasound images.

Although regular physical activity exposure leads to positive postural balance control (PBC) adaptations, few studies investigated its effects, or the one of inactivity, on PBC in populations of different age groups. Thus, this study investigated the impact of a physically active lifestyle on static and dynamic PBC in young and older adults. Thirty-five young physically active subjects (YA), 20 young sedentary subjects (YS), 16 physically active older adults (OA), and 15 sedentary older adults (OS) underwent a static and a dynamic PBC assessment. A force platform and an instrumented proprioceptive board were employed to measure the center of pressure (COP) trajectory and the anteroposterior oscillations, respectively. In static conditions, no significant differences were detected among groups considering the overall postural balance performance represented by the area of confidence ellipse values. Conversely, the YA highlighted a higher efficiency (i.e., lower sway path mean velocity) in PBC maintenance compared to the other groups (YA vs OA: p = 0.0057, Cohen’s d = 0.94; YA vs OS p = 0.043, d = 1.07; YA vs YS p = 0.08, d = 0.67). OS exhibited an overall worse performance in dynamic conditions than YA and YS. Surprisingly, no differences were found between YS and OA for all the static and dynamic parameters considered. In conclusion, our results suggest that a physically active lifestyle may promote static and dynamic balance performance in young and older adults, thus with potentially positive effects on the age-related decline of postural balance performance. Dynamic PBC assessment seems more sensitive in detecting differences between groups than the static evaluation.

Increased serial sarcomere number (SSN) has been observed in rats following downhill running training due to the emphasis on active lengthening contractions; however, little is known about the influence on dynamic contractile function. Therefore, we employed 4 weeks of weighted downhill running training in rats, then assessed soleus SSN and work loop performance. We hypothesised trained rats would produce greater net work output during work loops due to a greater SSN. Thirty-one Sprague-Dawley rats were assigned to a training or sedentary control group. Weight was added during downhill running via a custom-made vest, progressing from 5–15% body mass. Following sacrifice, the soleus was dissected, and a force-length relationship was constructed. Work loops (cyclic muscle length changes) were then performed about optimal muscle length (LO) at 1.5–3-Hz cycle frequencies and 1–7-mm length changes. Muscles were then fixed in formalin at LO. Fascicle lengths and sarcomere lengths were measured to calculate SSN. Intramuscular collagen content and crosslinking were quantified via a hydroxyproline content and pepsin-solubility assay. Trained rats had longer fascicle lengths (+13%), greater SSN (+8%), and a less steep passive force-length curve than controls (P0.05). Net work output was greater (+78–209%) in trained than control rats for the 1.5-Hz work loops at 1 and 3-mm length changes (P

Human skeletal muscle atrophy and a disproportionate force loss occur within a few days of unloading in space and on Earth, but the underlying mechanisms are not fully understood. Disruption of neuromuscular junction homeostasis has been proposed as one of the possible causes. Here, we investigated the potential mechanisms involved in this neuromuscular disruption induced by a 10-day unilateral lower limb suspension (ULLS) in humans. Specifically, we investigated hemichannels’ upregulation, neuromuscular junction and axonal damage, neurotrophins’ receptor downregulation and inflammatory transcriptional signatures. Biomarkers were evaluated at local and systemic levels. At the sarcolemmal level, changes were found to be associated with an increased expression of connexin 43 and pannexin-1. Upregulation of the inflammatory transcripts revealed by deep transcriptomics was found after 10 days of ULLS. The destabilisation of the neuromuscular junction was not accompanied by changes in the secretion of the brain-derived neurotrophic factor and neurotrophin-4, while their receptor, BDNF/NT growth factors receptor (TrkB), decreased. Furthermore, at 5 days of ULLS, there was already a significant upregulation of the serum neurofilament light chain concentration, an established clinical biomarker of axonal injury. At 10 days of ULLS, other biomarkers of early denervation processes appeared. Hence, short periods of muscle unloading induce sarcolemmal hemichannels upregulation, inflammatory transcripts upregulation, neuromuscular junction instability and axonal damage.

IntroductionThe insertion/deletion (I/D) polymorphism in the gene for the major regulator of vascular tone, angiotensin-converting enzyme-insertion/deletion (ACE-I/D) affects muscle capillarization and mitochondrial biogenesis with endurance training. We tested whether changes of leg muscle oxygen saturation (SmO2) during exhaustive exercise and recovery would depend on the aerobic fitness status and the ACE I/D polymorphism.MethodsIn total, 34 healthy subjects (age: 31.8 ± 10.2 years, 17 male, 17 female) performed an incremental exercise test to exhaustion. SmO2 in musculus vastus lateralis (VAS) and musculus gastrocnemius (GAS) was recorded with near-IR spectroscopy. Effects of the aerobic fitness status (based on a VO2peak cutoff value of 50 ml O2 min−1 kg−1) and the ACE-I/D genotype (detected by PCR) on kinetic parameters of muscle deoxygenation and reoxygenation were assessed with univariate ANOVA.ResultsDeoxygenation with exercise was comparable in VAS and GAS (p = 0.321). In both leg muscles, deoxygenation and reoxygenation were 1.5-fold higher in the fit than the unfit volunteers. Differences in muscle deoxygenation, but not VO2peak, were associated with gender-independent (p > 0.58) interaction effects between aerobic fitness × ACE-I/D genotype; being reflected in a 2-fold accelerated deoxygenation of VAS for aerobically fit than unfit ACE-II genotypes and a 2-fold higher deoxygenation of GAS for fit ACE-II genotypes than fit D-allele carriers.DiscussionAerobically fit subjects demonstrated increased rates of leg muscle deoxygenation and reoxygenation. Together with the higher muscle deoxygenation in aerobically fit ACE-II genotypes, this suggests that an ACE-I/D genotype-based personalization of training protocols might serve to best improve aerobic performance.

PurposeTo investigate the time-course of changes in knee-extensors muscle mass, architecture and function in response to plyometric training (PLT) performed on a novel training device, the Tramp-Trainer. This machine consists in a trampoline connected to an inclined sledge which allows the performance of repeated jumps while the subject is sitting on a chair.MethodsEight healthy males (173.6 ± 4.7 cm, 69.7 ± 13.5 kg, 25.3 ± 4.6 years) underwent 6 weeks of bilateral PLT on the tramp-trainer machine. Training was performed three times per week (between 120 and 150 bounces per session). Knee-extensor maximum voluntary torque (MVT) and power, quadriceps femoris (QF) volume (VOL), cross-sectional area from the 20% to the 60% of femur length and CSAmean, together with vastus lateralis (VL) architecture (fascicle length, Lf, and pennation angle, PA) were assessed after 2, 4, and 6 weeks of PLT.ResultsAll results are presented as changes versus baseline values. MVT increased by 17.8% (week 2, p < 0.001) and 22.2% (week 4, p < 0.01), respectively, and declined to 13.3% (p < 0.05) at week 6 of PLT. Power increased by 18.2% (week 4, p < 0.05) and 19.7% (week 6, p < 0.05). QF VOL increased by 4.7% (week 4, p < 0.05) and 5.8% (week 6, p < 0.01); VL VOL increased by 5.2%, (p < 0.05), 8.2%, (p < 0.01), and 9.6% (p < 0.05) at weeks 2, 4, and 6, respectively. An increase in Lf was detected already at wk 2 (2.2%, p < 0.05), with further increase at 4 and 6 weeks of PLT (4 and 4.4%, respectively, p < 0.01). PA increased by 5.8% (p < 0.05) at week 6. Significant positive correlations were found between CSAmean and Power (R2 = 0.46, p < 0.001) and between QF VOL and Power (R2 = 0.44, p < 0.024).ConclusionsPLT induced rapid increases in muscle volume, fascicle length, pennation angle, torque and power in healthy younger adults. Notably, changes in VL VOL and Lf were detectable already after 2 weeks, followed by increases in knee extensors VOL and power from week 4 of PLT. Since the increase in CSAmean and QF VOL cannot fully explain the increment in muscle power, it is likely that other factors (such as adaptations in neural drive or tendon mechanical properties) may have contributed to such fucntional changes.

IntroductionGene polymorphisms are associated with athletic phenotypes relying on maximal or continued power production and affect the specialization of skeletal muscle composition with endurance or strength training of untrained subjects. We tested whether prominent polymorphisms in genes for angiotensin converting enzyme (ACE), tenascin-C (TNC), and actinin-3 (ACTN3) are associated with the differentiation of cellular hallmarks of muscle metabolism and contraction in high level athletes.MethodsMuscle biopsies were collected from m. vastus lateralis of three distinct phenotypes; endurance athletes (n = 29), power athletes (n = 17), and untrained non-athletes (n = 63). Metabolism-, and contraction-related cellular parameters (such as capillary-to-fiber ratio, capillary length density, volume densities of mitochondria and intramyocellular lipid, fiber mean cross sectional area (MCSA) and volume densities of myofibrils) and the volume densities of sarcoplasma were analyzed by quantitative electron microscopy of the biopsies. Gene polymorphisms of ACE (I/D (insertion/deletion), rs1799752), TNC (A/T, rs2104772), and ACTN3 (C/T, rs1815739) were determined using high-resolution melting polymerase chain reaction (HRM-PCR). Genotype distribution was assessed using Chi2 tests. Genotype and phenotype effects were analyzed by univariate or multivariate analysis of variance and post hoc test of Fisher. P-values below 0.05 were considered statistically significant.ResultsThe athletes demonstrated the specialization of metabolism- and contraction-related cellular parameters. Differences in cellular parameters could be identified for genotypes rs1799752 and rs2104772, and localized post hoc when taking the interaction with the phenotype into account. Between endurance and power athletes these concerned effects on capillary length density for rs1799752 and rs2104772, fiber type distribution and volume densities of myofibrils (rs1799752), and MSCA (rs2104772). Endurance athletes carrying the I-allele of rs1799752 demonstrated 50%-higher volume densities of mitochondria and sarcoplasma, when power athletes that carried only the D-allele showed the highest fiber MCSAs and a lower percentage of slow type muscle fibers.DiscussionACE and tenascin-C gene polymorphisms are associated with differences in cellular aspects of muscle metabolism and contraction in specifically-trained high level athletes. Quantitative differences in muscle fiber type distribution and composition, and capillarization in knee extensor muscle explain, in part, identified associations of the insertion/deletion genotypes of ACE (rs1799752) with endurance- and power-type Sports.

The preservation of muscle power is crucial in aging for maintaining mobility and performing daily tasks. Resistance training involving high movement velocities represents a valid strategy to slow down the rate of sarcopenia, counteracting the loss of muscle mass and muscle power. Plyometric exercise may represent an effective training modality for increasing muscle power; however, its application in older populations has been sparingly investigated, as the high impact actions involved may reduce its feasibility for older individuals. By adopting a safer modality of plyometric training, we investigated if a 6-week plyometric training intervention could increase knee extensor muscle size, architecture, force and power in 14 young (YM, age = 25.4 ± 3.5 y; means ± SD) and nine older males (OM, age = 69.7 ± 3.4 y). Volunteers trained 3 times/week using a device similar to a leg press machine where the user was required to bounce against his body mass on a trampoline. Pre-to-post training changes in isometric maximum voluntary torque (MVT), leg extension power and vastus lateralis (VL) architecture were assessed. Muscle power increased in both groups (+27% OM -P < 0.001, 20% YM -P < 0.001), although the total external work performed during the training period was significantly lower for OM (i.e., ~-47%). Both groups showed significant increases in muscle thickness (MT) (+5.8 OM -P < 0.01 vs. +3.8% YM -P < 0.01), fascicle length (Lf) (+8% OM -P < 0.001 vs. +6% YM -P < 0.001), and pennation angle (PA) (+7.5% OM -P < 0.001 vs. +4.1% YM -P < 0.001). The current study shows that trampoline-based plyometric training is an effective intervention producing a rapid increase in muscle mass and power in both young and older individuals. The training modality used in this study seems to particularly benefit the older population, targeting the morphological and functional effects of sarcopenia in human muscle.

Competitive alpine skiers are subject to substantial risks of injury, especially concerning the anterior cruciate ligament (ACL). During “landing back weighted” episodes, hamstrings may partially counteract the anterior shear force acting on the tibia by eccentrically resisting the boot-induced drawer of the tibia relative to the femur. The aim of the present study was to provide novel descriptive data and sport-specific reference values on maximal eccentric hamstrings strength (MEHS) in competitive alpine skiers from youth to elite level, and to explore potential relationships with sex, age and biological maturation. 170 competitive alpine skiers were investigated: 139 youth athletes (51 females, 88 males; age: 13.8 ± 0.59 years) and 31 elite athletes (19 females, 12 males; age: 21.7 ± 2.8 years). MEHS was assessed by the (Vald Performance, Newstead, Australia). U15 female skiers presented lower MEHS compared to female elite skiers for both limbs (R = 210 ± 44 N vs. 340 ± 48 N, respectively, p < 0.001, and L = 207 ± 46 N vs. 303 ± 35 N, respectively, p < 0.001). Similarly, lower MEHS was observed in U15 male skiers compared to male elite skiers for both limbs (R = 259 ± 51 N vs. 486 ± 62 N, respectively, p < 0.001, and L = 258 ± 57 N vs. 427 ± 54 N, respectively, p < 0.001). Correlations between MEHS and chronological age were modestly significant only for the U15 group (r = 0.37 and p < 0.001). When the correlations for the U15 group were performed between MHES and maturity offset (obtained from the calculation of biological age, i.e., age at peak height velocity), statistical significance was reached by all the correlations run for 3 variables (Males < 0: r = 0.59, p < 0.0001; Males > 0: r = 0.70, p < 0.0001; and Females > 0: r = 0.46, p < 0.0001, start of maturity offset = 0). This cross-sectional description of MEHS in alpine skiers from youth to elite level highlights the importance of biological maturation for MEHS values in youth athletes and presents novel data that may offer insights into new approaches for injury prevention.

Ultrasound-based shear wave elastography (SWE) provides the means to quantify tissue mechanical properties in vivo and has proven valuable in detecting degenerative processes in tendons. Its current mode of use is for two-dimensional rendering measurements, which are highly position-dependent. We therefore propose an approach to create a volumetric reconstruction of the mechano-acoustic properties of a structure of interest based on optically tracking the ultrasound probe during free-hand measurement sweeps. In the current work, we aimed (1) to assess the technical feasibility of the three-dimensional mapping of unidirectional shear wave velocity (SWV), (2) to evaluate the possible artefacts associated with hand-held image acquisition, (3) to investigate the reproducibility of the proposed technique, and (4) to study the potential of this method in detecting local adaptations in a longitudinal study setting. Operative and technical feasibility as well as potential artefacts associated with hand-held image acquisition were studied on a synthetic phantom containing discrete targets of known mechanical properties. Measurement reproducibility was assessed based on inter-day and inter-reader scans of the patellar, Achilles, and supraspinatus tendon of ten healthy volunteers and was compared to traditional two-dimensional image acquisition. The potential of this method in detecting local adaptations was studied by testing the effect of short-term voluntary isometric loading history on SWV along the tendon long axis. The suggested approach was technically feasible and reproducible, with a moderate to very good reliability and a standard error of measurement in the range of 0.300–0.591 m/s for the three assessed tendons at the two test-retest modalities. We found a consistent variation in SWV along the longitudinal axis of each tendon, and isometric loading resulted in regional increases in SWV in the patellar and Achilles tendons. The proposed method outperforms traditional two-dimensional measurement with regards to reproducibility and may prove valuable in the objective assessment of pathological tendon changes.

We investigated molecular and cellular parameters which set metabolic and mechanical functioning of knee extensor muscles in the operated and contralateral control leg of 9 patients with a chronically insufficient anterior cruciate ligament (ACL; 26.6 ± 8.3 years, 8 males, 1 female) after open reconstructive surgery (week 0), after ambulant physiotherapy under cast immobilization (week 9), succeeding rehabilitation training (up to week 26), and subsequent voluntary physical activity (week 260). Clinical indices of knee function in the operated leg were improved at 52 weeks and remained at a comparable level at week 260. CSA of the quadriceps (-18%), MCSA of muscle fibers (-24%), and capillary-to-fiber ratio (-24%) in m. vastus lateralis from the ACL insufficient leg were lower at week 0 than reference values in the contralateral leg at week 260. Slow type fiber percentage (-35%) and mitochondrial volume density (-39%) were reduced in m. vastus lateralis from the operated leg at weeks 9 and 26. Composition alterations in the operated leg exceeded those in the contralateral leg and, with the exception of the volume density of subsarcolemmal mitochondria, returned to the reference levels at week 260. Leg-specific deterioration of metabolic characteristics in the vasti from the operated leg was reflected by the down-regulation of mitochondrial respiration complex I-III markers (-41–57%) at week 9. After rehabilitation training at week 26, the specific Y397 phosphorylation of focal adhesion kinase (FAK), which is a proxy for mechano-regulation, was elevated by 71% in the operated leg but not in the contralateral leg, which had performed strengthening type exercise during ambulant physiotherapy. Total FAK protein and Y397 phosphorylation levels were lowered in both legs at week 26 resulting in positive correlations with mitochondrial volume densities and mitochondrial protein levels. The findings emphasize that a loss of mechanical and metabolic characteristics in knee extensor muscle remains detectable years after untreated ACL rupture, which may be aggravated in the post-operative phase by the deterioration of slow-oxidative characteristics after reconstruction due to insufficient load-bearing muscle activity. The reestablishment of muscle composition subsequent to years of voluntary physical activity reinforces that slow-to-fast fiber transformation is reversible in humans.

Non-specific chronic low back pain (nsCLBP) is a multifactorial condition of unknown etiology and pathogenesis. Physical and genetic factors may influence the predisposition of individuals to CLBP, which in many instances share a musculoskeletal origin. A reduced pain level in low back pain patients that participate in exercise therapy highlights that disuse-related muscle deconditioning may predispose individuals to nsCLBP. In this context, musculoskeletal pain may be the consequence of capillary rarefaction in inactive muscle as this would lower local tissue drainage and washing out of toxic waste. Muscle activity is translated into an angio-adaptative process, which implicates angiogenic-gene expression and individual response differences due to heritable modifications of such genes (gene polymorphisms). The pathophysiologic mechanism underlying nsCLBP is still largely unaddressed. We hypothesize that capillary rarefaction due to a deconditioning of dorsal muscle groups exacerbates nsCLBP by increasing noxious sensation, reducing muscle strength and fatigue resistance by initiating a downward spiral of local deconditioning of back muscles which diminishes their load-bearing capacity. We address the idea that specific factors such as angiotensin-converting enzyme and Tenascin-C might play an important role in altering susceptibility to nsCLBP via their effects on microvascular perfusion and vascular remodeling of skeletal muscle, inflammation, and pain sensation. The genetic profile may help to explain the individual predisposition to nsCLBP, thus identifying subgroups of patients, which could benefit from ad hoc treatment types. Future therapeutic approaches aimed at relieving the pain associated with nsCLBP should be based on the verification of mechanistic processes of activity-induced angio-adaptation and muscle-perfusion.

Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively); however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric actions generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT) is assumed to produce greater hypertrophy than concentric resistance training (CON RT). Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood.Thus, the present review aims to, (a) critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b) clarify the molecular mechanisms that may regulate such adaptations.We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions.

The purpose of this short review is to discuss the effects of eccentric exercise in modifying the properties of tendon tissue in healthy individuals. The tendon provides a mechanical link between muscle and bone, allowing force transmission to the skeleton, and thus, its properties have significant functional implications. Chronic resistance training has long been shown to increase the stiffness and Young’s modulus of the tendon and even tendon cross-sectional area. However, as the tendon responds to the amount and/or frequency of strain, it has been previously suggested that eccentric training may result in greater adaptations due to the potential for greater training loads. Thus, this review discusses the effects of eccentric training upon healthy tendon tissue and compares these to other training modalities. Furthermore, it has been reported that the tendon may undergo adverse age-related changes. Thus, this review also discusses the potential application of eccentric resistance training as a preferential modality for counteracting these age-related changes. We conclude that while there may be no difference between contraction types for overall tendon adaptation, the lower demands of eccentric contractions may make it more appealing for the elderly population.